Reproduction Hack Makes Mice From Two Dads

In a weird feat of biotechnological virtuosity, scientists have engineered mice with genes from two dads, and none from a mom.

This was done by engineering females with eggs containing only chromosomes from a father. Mating added genes from a second father.

“These findings have novel implications for mammalian reproduction and assisted-reproductive technology,” wrote researchers led by University of Texas geneticist Richard Behringer in a study published December 8 in Biology of Reproduction.

The findings are the latest in a string of strange reproduction tricks, including human embryos with DNA from three parents and cloned monkeys with genes from two mothers.

Those techniques, both of which are still far from practical or legal human use — and may never be used — are focused on preventing the transmission of inheritable genetic disorders.

Likewise, the double-dad technique could “conceivably provide a way to bypass the inheritance of mitochondrial disease theoretically,” though logistical and ethical challenges make it extremely unlikely. It could, however, be used in breeding prize livestock or rare animals.

The researchers started with a line of induced pluripotent cells — cells that have been genetically reprogrammed into a stem cell-like state — from a male mouse, or Dad No. 1.

In about 1 percent of these cells, natural mistakes in cell division eliminated the Y-chromosome. (Male cells have two strands of chromosomes, X and Y, while female cells have two X-chromosomes.)

The DNA was then removed from these X-only cells, and injected into immature embryos, which were transplanted into a surrogate mother.

The resulting offspring had only X-chromosomes: two from the mother, and one from Dad No. 1. Among female offspring, some of their eggs contained only Dad No. 1’s chromosomes.

When they mated, those eggs met the sperm of Dad No. 2. The resulting offspring had two dads.

A major impediment to any use of this technique, even in animals, is the tendency of reprogrammed cells to become cancerous.

Impediments aside, it may be possible to use reprogramming “to generate sperm from a female donor,” wrote the researchers, “and produce viable male and female progeny with two mothers.”

Image: Arrow at left points to an engineered female with eggs containing DNA from a male, surrounded by her progeny; arrows at left point to a female and her mate, surrounded by their progeny. /Biology of Reproduction.

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